Why we want to sequence your ass

I’ve been rounding in the hospital on about 30 very sick patients every day for 2 weeks as attending physician on the Leukemia and Stem Cell Transplant Service. It’s one intense experience. I enjoy the intellectual challenge of supervising a team of doctors and nurses dealing with hundreds of extremely complex medical decisions. They only give me the hard ones. Emotionally, the experience is even more challenging. Patients on our service have fatal, nasty diseases, but stem cell transplant medicine brings them here hoping for a cure. Facing these patients and their families when things don’t go well, when the disease relapses, when complications set in is the hardest part of this job. As the attending doc, the buck stops with me. The staff, patients and families look to me for answers to impossible questions.

My colleagues and I have been using new sequencing technology to try and cure cancer, the same tech has allowed scientists to study our microbiomes: the bacteria, fungi and viruses that live all over us and in us. It’s super-cool science, because microbiologists have traditionally relied on culture to identify germs, but “metagenomics” allows characterization of our beasties straight away and therefore might be able to give a more detailed and accurate picture of the life on our bodies. I’m jaded when it comes to the claims of scientists regarding “translation” to clinical care in the near future. But in this case, we need this technology in the clinic right away.

Our patients have immune systems that have been devastated by bone marrow failure syndromes, leukemia and our treatments. These folks have severe immunosuppression and are susceptible to opportunistic bacterial, fungal and viral infections like nobody’s business.

I tell the fellows on bone marrow transplant the differential diagnosis of ANY symptom is “sepsis, sepsis, sepsis and sepsis.”

Image

Clostridium difficile, a nasty bacteria that causes diarrhea and colitis in patients whose normal intestinal flora have been disrupted by antibiotics and immune suppression.

I approached Dr. George Weinstock at a meeting and told him that if he wanted to see huge shifts in human microbiota, he should check out our hematopoietic stem cell transplant patients. Today, we treat our patients largely empirically–often, we don’t know what infections we’re treating, we use “gorillacilin,” broad-spectrum antibiotics that target germs like a shotgun.

George was intrigued, and we gathered additional colleagues and we are starting to collaborate. Dr. Mark Schroeder another bone marrow transplant physician-researcher at Wash U is heading up the clinical trial. Our plan at this stage is to characterize the microbiomes of patients undergoing stem cell transplants and get a feel for what the technology can detect using real clinical specimens.

There is a young man with aplastic anemia right now very sick with infection by an unknown organism(s). We are giving him broad-spectrum antibiotics, but his immune system is destroyed and lack of white blood cells has made him a target for all variety of opportunistic organisms. We are trying to keep the man alive until we can get him his stem cell transplant–he needs a new immune system. Why can’t we use state-of-the-art DNA sequencing technology to tailor his antibiotic regimen today? Target bad germs early and specifically? The situation is desperate. Why is this technology not here where it needs to be?

5 thoughts on “Why we want to sequence your ass

  1. I don’t know the answer to your last question, but it sounds like your group is making great strides toward a practical application of this technology. Bravo.

    • The Oy, was about the predicament, not your approach. But something that occurred to me is that by sequencing the gut microbiome you might miss other sources of infection that may not have colonized there, no? Like connective tissue, sinuses, etc.

      • Certainly. The gut is the most accessible (diarrhea), but other samples will be collected. The money will most likely be where the site of infection seems to dwell.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s